The use of certain polyethoxylated ether derivatives of castor oil as surfactants and/or emulsifiers in topical ophthalmic formulations is known. See Hata, Murano, and Ueda, CA 118:261059, Ophthalmic solutions containing cyclosporin and surfactants; Koide, CA 122:17250, Vitamin A-solubilized eye drops; Fukahori, Uchino, and Takahashi, CA 118:109767, Aqueous vitamin E solutions containing surfactants; Fukahori, Takahashi, and Uchino, CA 114:254038, Stable eye drops containing vitamin E, FAD sodium salt, allantoin, and glycyrrhizin; Takahashi, Fukahori, Uchino, and Eino, CA 114:254039, Stable FAD sodium salt or cyanocobalamine eye drops; Koide and Kojima, CA 120:86468, Stable eyedrops of naphazoline containing nonionic surfactants and glycyrrhizinate salts; Koide, CA 121:91816, Stable solutions containing solubilized vitamin A derivatives; Nagy, U.S. Pat. No. 4,960,799, Stabilized Aqueous Solutions of Pharmaceutically Acceptable Salts of Ortho-(2,6-Dichtorophenyl)-Amino-Phenylacetic Acid for Ophthalmic Use, Oct. 2, 1990 and related Product Insert for Voltaren Ophthalmic; Doulakas, U.S. Pat. No. 4,829,088, Medicament for the Treatment of Inflammations of the Eye, May 9, 1989; and Koide and Aoshima, CA 121:308384, Stable Vitamin A- and E-solubilized eye drops.
The use of carbonic anhydrase inhibitors (CAIs) in topical ophthalmic formulations for lowering intraocular pressure is known. See, for example, U.S. Pat. Nos. 5,153,192; 5,240,923; 5,378,703; and 4,797,413. Although CAIs are very useful in lowering intraocular pressure, they are typically difficult to formulate at physiological pH due to their sparing solubility except at uncomfortably low pHs. Formulation has also proved challenging due to the instability of some CAIs.
The compositions of the present invention overcome the problems associated with prior CAI compositions in that they are comfortable and stable.